DEOXYSPERGUALIN SUPPRESSES LOCAL MACROPHAGE PROLIFERATION IN RAT RENAL-ALLOGRAFT REJECTION

Deoxyspergualin (DSP) is a potent immunosuppressive drug that is able to both prevent and reverse acute allograft rejection. Although there is good evidence that DSP can inhibit T and B lymphocyte responses, th e effect of this drug upon monocyte function is controversial. In the current study, substantial local proliferation of inflammatory macroph ages (41.6+/-5.5% of ED1(+) cells) within acutely rejecting rat renal allografts was identified by expression of the proliferating cell nucl ear antigen. Treatment of animals with DSP not only reduced macrophage accumulation within the tissue, but it also significantly inhibited l ocal proliferation of macrophages within the graft (26.4+/-5.6% of ED1 (+) cells, P<0.05 vs. untreated). This appeared to be, at least in par t, a direct effect of DSP upon macrophages since the drug also inhibit ed growth of 2 monocytic cell lines (RC-2A and U937) in vitro. However , DSP treatment had no effect upon LPS-induced monocyte IL-1 beta, TNF alpha, and IL-6 mRNA and protein production, indicating that this dru g is not a general inhibitor of monocyte function. In conclusion, this study has demonstrated that local proliferation of macrophages within the kidney is a prominent feature of acute allograft rejection and th at inhibition of this response is one mechanism whereby DSP exerts its potent immunosuppressive actions.